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https://www.readbyqxmd.com/read/28525906/copy-number-variations-of-circulating-cell-free-dna-in-urothelial-carcinoma-of-the-bladder-patients-treated-with-radical-cystectomy-a-prospective-study
#1
Armin Soave, Felix K-H Chun, Timo Hillebrand, Michael Rink, Lars Weisbach, Bettina Steinbach, Margit Fisch, Klaus Pantel, Heidi Schwarzenbach
The aim of the present study was to establish a rapid profiling method using multiplex ligation-dependent probe amplification (MLPA) and characterize copy number variations (CNV) in circulating, cell-free DNA (cfDNA) in 85 urothelial carcinoma of the bladder (UCB) patients treated with radical cystectomy (RC). MLPA was tested for the use of cfDNA extracted from serum and plasma by various commercial extraction kits. Eighteen probes served as reference to control denaturation, ligation and amplification efficiency...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28522829/somatic-tumor-mutations-detected-by-targeted-next-generation-sequencing-in-minute-amounts-of-serum-derived-cell-free-dna
#2
Marjolein J A Weerts, Ronald van Marion, Jean C A Helmijr, Corine M Beaufort, Niels M G Krol, Anita M A C Trapman-Jansen, Winand N M Dinjens, Stefan Sleijfer, Maurice P H M Jansen, John W M Martens
The use of blood-circulating cell-free DNA (cfDNA) as 'liquid-biopsy' is explored worldwide, with hopes for its potential in providing prognostic or predictive information in cancer treatment. In exploring cfDNA, valuable repositories are biobanks containing material collected over time, however these retrospective cohorts have restrictive resources. In this study, we aimed to detect tumor-specific mutations in only minute amounts of serum-derived cfDNA by using a targeted next generation sequencing (NGS) approach...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28521774/correlation-of-cell-free-dna-plasma-concentration-with-severity-of-non-alcoholic-fatty-liver-disease
#3
Thomas Karlas, Lara Weise, Stephanie Kuhn, Felix Krenzien, Matthias Mehdorn, David Petroff, Nicolas Linder, Alexander Schaudinn, Harald Busse, Volker Keim, Johann Pratschke, Johannes Wiegand, Katrin Splith, Moritz Schmelzle
BACKGROUND: The assessment of fibrosis and inflammatory activity is essential to identify patients with non-alcoholic fatty liver disease (NAFLD) at risk for progressive disease. Serum markers and ultrasound-based methods can replace liver biopsy for fibrosis staging, whereas non-invasive characterization of inflammatory activity remains a clinical challenge. Cell-free DNA (cfDNA) is a novel non-invasive biomarker for assessing cellular inflammation and cell death, which has not been evaluated in NAFLD...
May 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28514925/factors-affecting-cell-free-dna-fetal-fraction-and-the-consequences-for-test-accuracy
#4
Fergus Perry Scott, Melody Menezes, Ricardo Palma-Dias, Debbie Nisbet, Philip Schluter, Fabricio da Silva Costa, Andrew Cameron McLennan
INTRODUCTION: Biological factors are known to influence the fetal fraction (FF) of cell-free DNA and may also influence the accuracy of non-invasive prenatal testing. MATERIAL AND METHODS: NIPT from 5,267 mixed risk women across three specialist clinics in Australia were analysed. Multivariable regression analysis was used to determine whether maternal characteristics, ultrasound and placental biomarkers affect FF and test accuracy. RESULTS: FF ranged from 4% - 37% (mean 11...
May 17, 2017: Journal of Maternal-fetal & Neonatal Medicine
https://www.readbyqxmd.com/read/28511612/ngs-analysis-on-tumor-tissue-and-cfdna-for-genotype-directed-therapy-in-metastatic-nsclc-patients-between-hope-and-hype
#5
Alexander T Falk, Simon Heeke, Véronique Hofman, Virginie Lespinet, Camille Ribeyre, Olivier Bordone, Michel Poudenx, Josiane Otto, Georges Garnier, Olivier Castelnau, Joël Guigay, Sylvie Leroy, Charles-Hugo Marquette, Paul Hofman, Marius Ilié
The advent of genomic based precision medicine led to the implementation of biomarker testing in metastatic non-small cell lung cancer (NSCLC) patients. Next generation sequencing (NGS) has been recently implemented to routine diagnostic requirements in lung oncology. Areas covered: Two cases of patients with metastatic NSCLC for whom NGS analysis performed on both tumor and liquid biopsy has not improved the clinical course of their disease are reported. These cases illustrate the difficulty of the so-called "personalized or precision" medicine in clinical routine practice for metastatic NSCLC...
May 17, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28506684/study-of-preanalytic-and-analytic-variables-for-clinical-next-generation-sequencing-of-circulating-cell-free-nucleic-acid
#6
Meenakshi Mehrotra, Rajesh R Singh, Wei Chen, Richard S P Huang, Alaa A Almohammedsalim, Bedia A Barkoh, Crystal M Simien, Marcos Hernandez, Carmen Behrens, Keyur P Patel, Mark J Routbort, Russell R Broaddus, L Jeffrey Medeiros, Ignacio I Wistuba, Scott Kopetz, Rajyalakshmi Luthra
Detection of mutations in plasma circulating cell-free DNA (cfDNA) by next-generation sequencing (NGS) has opened up new possibilities for monitoring treatment response and disease progression in patients with solid tumors. However, implementation of cfDNA genotyping in diagnostic laboratories requires systematic assessment of preanalytical parameters and analytical performance of NGS platforms. We assessed the effects of peripheral blood collection tube and plasma separation time on cfDNA yield and integrity and performance of the Ion PGM, Proton, and MiSeq NGS platforms...
May 12, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28504856/cell-free-dna-copy-number-variations-in-plasma-from-colorectal-cancer-patients
#7
Jian Li, Rachel L Dittmar, Shu Xia, Huijuan Zhang, Meijun Du, Chiang-Ching Huang, Brooke R Druliner, Lisa Boardman, Liang Wang
To evaluate clinical utility of cell free DNA (cfDNA), we performed whole genome sequencing to systematically examine plasma cfDNA copy number variations (CNVs) in a cohort of patients with colorectal cancer (CRC, n=80), polyps (n=20) and healthy controls (n=35). We initiallycompared cfDNA yield in 20 paired serum-plasma samples and observed significantly higher cfDNA concentration in serum (median=81.20ng, range 7.18-500ng/ml) than in plasma (median=5.09ng, range 3.76-62.8ng/ml) (p<0.0001). However, tumor-derived cfDNA content was significantly lower in serum than in matched plasma samples tested...
May 15, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28502728/technical-validation-of-a-next-generation-sequencing-assay-for-detecting-clinically-relevant-levels-of-breast-cancer-related-single-nucleotide-variants-and-copy-number-variants-using-simulated-cell-free-dna
#8
Xin Yang, Yuxing Chu, Rui Zhang, Yanxi Han, Lucheng Zhang, Yu Fu, Dan Li, Rongxue Peng, Dongdong Li, Jiansheng Ding, Ziyang Li, Meiru Zhao, Kuo Zhang, Tian Lu, Lang Yi, Qisheng Wu, Guigao Lin, Jiehong Xie, Tao Liu, Ling Yang, Xin Yi, Jinming Li
Next-generation sequencing (NGS) is commonly used in a clinical setting for diagnostic and prognostic testing of genetic mutations to select optimal targeted therapies. Herein, we describe the development of a custom NGS assay for detecting single-nucleotide variants (SNVs) and copy number variations (CNVs) in a panel of 51 genes related to breast cancer. We designed and implemented a validation strategy in accordance with principles and guidelines developed by the Next-Generation Sequencing: Standardization of Clinical Testing work group using artificial, cell-free DNA (cfDNA) with mutant fragments prepared in a simple, rapid, and cost-effective manner...
May 11, 2017: Journal of Molecular Diagnostics: JMD
https://www.readbyqxmd.com/read/28500398/comparative-clinical-utility-of-tumor-genomic-testing-and-cell-free-dna-in-metastatic-breast-cancer
#9
Kara N Maxwell, Danielle Soucier-Ernst, Emin Tahirovic, Andrea B Troxel, Candace Clark, Michael Feldman, Christopher Colameco, Bijal Kakrecha, Melissa Langer, David Lieberman, Jennifer J D Morrissette, Matt R Paul, Tien-Chi Pan, Stephanie Yee, Natalie Shih, Erica Carpenter, Lewis A Chodosh, Angela DeMichele
PURPOSE: Breast cancer metastases differ biologically from primary disease; therefore, metastatic biopsies may assist in treatment decision making. Commercial genomic testing of both tumor and circulating tumor DNA have become available clinically, but utility of these tests in breast cancer management remains unclear. METHODS: Patients undergoing a clinically indicated metastatic tumor biopsy were consented to the ongoing METAMORPH registry. Tumor and blood were collected at the time of disease progression before subsequent therapy, and patients were followed for response on subsequent treatment...
May 12, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28492524/sociodemographic-and-attitudinal-predictors-of-simultaneous-and-redundant-multiple-marker-and-cell-free-dna-screening-among-women-aged-%C3%A2-35-years
#10
A K Lewkowitz, A J Kaimal, K Thao, A O'Leary, O Nseyo, M Kuppermann
OBJECTIVE: To identify characteristics associated with undergoing cell-free DNA (cfDNA) and multiple marker screening (MMS) simultaneously or redundantly (after receiving negative results from the first screening test) among women aged ⩾35 years. STUDY DESIGN: Participants presenting for prenatal testing completed a questionnaire that included measures of pregnancy worry and attitudes toward potential testing outcomes; data on prenatal test use was obtained via medical record review...
May 11, 2017: Journal of Perinatology: Official Journal of the California Perinatal Association
https://www.readbyqxmd.com/read/28492516/circulating-cell-free-dna-and-circulating-tumor-cells-as-prognostic-and-predictive-biomarkers-in-advanced-non-small-cell-lung-cancer-patients-treated-with-first-line-chemotherapy
#11
Simona Coco, Angela Alama, Irene Vanni, Vincenzo Fontana, Carlo Genova, Maria Giovanna Dal Bello, Anna Truini, Erika Rijavec, Federica Biello, Claudio Sini, Giovanni Burrafato, Claudia Maggioni, Giulia Barletta, Francesco Grossi
Cell-free DNA (cfDNA) and circulating tumor cells (CTCs) are promising prognostic and predictive biomarkers in non-small cell lung cancer (NSCLC). In this study, we examined the prognostic role of cfDNA and CTCs, in separate and joint analyses, in NSCLC patients receiving first line chemotherapy. Seventy-three patients with advanced NSCLC were enrolled in this study. CfDNA and CTC were analyzed at baseline and after two cycles of chemotherapy. Plasma cfDNA quantification was performed by quantitative PCR (qPCR) whereas CTCs were isolated by the ScreenCell Cyto (ScreenCell, Paris, France) device and enumerated according to malignant features...
May 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28492226/circulating-tumour-dna-sequence-analysis-as-an-alternative-to-multiple-myeloma-bone-marrow-aspirates
#12
Olena Kis, Rayan Kaedbey, Signy Chow, Arnavaz Danesh, Mark Dowar, Tiantian Li, Zhihua Li, Jessica Liu, Mark Mansour, Esther Masih-Khan, Tong Zhang, Scott V Bratman, Amit M Oza, Suzanne Kamel-Reid, Suzanne Trudel, Trevor J Pugh
The requirement for bone-marrow aspirates for genomic profiling of multiple myeloma poses an obstacle to enrolment and retention of patients in clinical trials. We evaluated whether circulating cell-free DNA (cfDNA) analysis is comparable to molecular profiling of myeloma using bone-marrow tumour cells. We report here a hybrid-capture-based Liquid Biopsy Sequencing (LB-Seq) method used to sequence all protein-coding exons of KRAS, NRAS, BRAF, EGFR and PIK3CA in 64 cfDNA specimens from 53 myeloma patients to >20,000 × median coverage...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28489509/akt-inhibition-in-solid-tumors-with-akt1-mutations
#13
David M Hyman, Lillian M Smyth, Mark T A Donoghue, Shannon N Westin, Philippe L Bedard, Emma J Dean, Hideaki Bando, Anthony B El-Khoueiry, José A Pérez-Fidalgo, Alain Mita, Jan H M Schellens, Matthew T Chang, Jonathan B Reichel, Nancy Bouvier, S Duygu Selcuklu, Tara E Soumerai, Jean Torrisi, Joseph P Erinjeri, Helen Ambrose, J Carl Barrett, Brian Dougherty, Andrew Foxley, Justin P O Lindemann, Robert McEwen, Martin Pass, Gaia Schiavon, Michael F Berger, Sarat Chandarlapaty, David B Solit, Udai Banerji, José Baselga, Barry S Taylor
Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary activity of AKT inhibition in AKT-mutant cancers. Patients and Methods Fifty-eight patients with advanced solid tumors were treated. The primary end point was safety; secondary end points were progression-free survival (PFS) and response according to Response Evaluation Criteria in Solid Tumors (RECIST)...
May 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28485169/plasma-cell-free-dna-integrity-plus-circulating-tumor-cells-a-potential-biomarker-of-no-distant-metastasis-breast-cancer
#14
W Wang, M Liang, G Ma, L Li, W Zhou, T Xia, H Xie, S Wang
Cell-free DNA integrity (cfDI) is a promising diagnostic and prognostic biomarker in breast cancer. However, no specific study has evaluated the diagnostic ability of cfDI in patients with no distant metastasis breast cancer (no-MBC) and benign breast tumor (BBT) to date. We assessed the plasma cfDI of 84 patients with no-MBC and 30 patients with BBT using quantitative PCR and compared it with circulating tumor cells (CTCs) and carbohydrate antigen 153 (CA153). The no-MBC group had significantly lower mean cfDI (0...
May 9, 2017: Neoplasma
https://www.readbyqxmd.com/read/28468865/cell-free-dna-from-ascites-and-pleural-effusions-molecular-insights-into-genomic-aberrations-and-disease-biology
#15
Hatim Husain, David Nykin, Nam Bui, Daniel Quan, German Gomez, Brian Woodward, Sumathi Venkatapathy, Radha Duttagupta, Eric Fung, Scott M Lippman, Razelle Kurzrock
Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number variations (CNV) were discovered within the effusate. One individual had a relevant alteration with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only MDM2 and CDK4 amplification in a prior tissue biopsy...
May 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28460452/value-of-circulating-cell-free-dna-analysis-as-a-diagnostic-tool-for-breast-cancer-a-meta-analysis
#16
Ziqiang Lin, James Neiswender, Bin Fang, Xuelei Ma, Jing Zhang, Xiuying Hu
OBJECTIVES: The aim of this study was to systematically evaluate the diagnostic value of cell free DNA (cfDNA) for breast cancer. RESULTS: Among 308 candidate articles, 25 with relevant diagnostic screening qualified for final analysis. The mean sensitivity, specificity and area under the curve (AUC) of SROC plots for 24 studies that distinguished breast cancer patients from healthy controls were 0.70, 0.87, and 0.9314, yielding a DOR of 32.31. When analyzed in subgroups, the 14 quantitative studies produced sensitivity, specificity, AUC, and a DOR of 0...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28457334/plasma-dna-and-rna-differentially-impact-coagulation-during-abdominal-sepsis-an-explorative-study
#17
Emmanuel Schneck, Omar Samara, Christian Koch, Andreas Hecker, Winfried Padberg, Christoph Lichtenstern, Markus Alexander Weigand, Florian Uhle
BACKGROUND: Cell-free DNA (cfDNA) and extracellular RNA (exRNA) are both suspected to activate coagulation cascades in sepsis. Therefore, our study investigated the influence of plasmatic nucleic acids on coagulation in septic patients in comparison to patients after major abdominal surgery. MATERIALS AND METHODS: A total of 15 patients with sepsis, 10 postoperative patients, and 10 healthy volunteers were included in this longitudinal study. Blood was collected at sepsis onset and after surgery respectively, as well as after 24, 72 and 168 h...
April 2017: Journal of Surgical Research
https://www.readbyqxmd.com/read/28454757/no-343-routine-non-invasive-prenatal-prediction-of-fetal-rhd-genotype-in-canada-the-time-is-here
#18
Jo-Ann Johnson, Kim MacDonald, Gwen Clarke, Amanda Skoll
The optimal management of the D-negative pregnant woman is now based on the non-invasive antenatal prediction of fetal D-blood group by cell-free DNA (cfDNA) in maternal plasma, with targeted prophylaxis for women carrying RHD-positive fetuses. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. This paper is the result of a consensus meeting of the Canadian National Rh Working Group, an interdisciplinary group formed to review the current status of fetal RHD genotyping based on cfDNA in Canada...
May 2017: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
https://www.readbyqxmd.com/read/28450567/circulating-tumor-dna-reflects-tumor-metabolism-rather-than-tumor-burden-in-chemotherapy-naive-patients-with-advanced-non-small-cell-lung-cancer-nsclc-an-18-f-fdg-pet-ct-study
#19
Silvia Morbelli, Angela Alama, Giulia Ferrarazzo, Simona Coco, Carlo Genova, Erica Rijavec, Francesca Bongioanni, Federica Biello, Maria Giovanna Dal Bello, Giulia Barletta, Michela Massollo, Irene Vanni, Roberta Piva, Alberto Nieri, Matteo Bauckneht, Gianmario Sambuceti, Francesco Grossi
We aimed to evaluate the relationship between Circulating tumor Cells (CTCs) and plasma Cell-free DNA (cfDNA) on one side and a comprehensive range of (18)F-fluorodeoxyglucose (FDG)-PET/CT-derived parameters on the other side in chemotherapy-naïve patients with advanced NSCLC. Methods: Among the seventy-nine patients included in the VeriStrat® trial (evaluating the role of pretreatment circulating tumor markers as predictors of prognosis), we selected patients submitted to FDG-PET/CT for clinical reasons just before the inclusion in the trial...
April 27, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28450425/circulating-free-dna-to-guide-prostate-cancer-treatment-with-parp-inhibition
#20
Jane Goodall, Joaquin Mateo, Wei Yuan, Helen Mossop, Nuria Porta, Susana Miranda, Raquel Perez-Lopez, David Dolling, Dan R Robinson, Shahneen Sandhu, Gemma Fowler, Berni Ebbs, Penny Flohr, George Seed, Daniel Nava Rodrigues, Gunther Boysen, Claudia Bertan, Mark Atkin, Matthew Clarke, Mateus Crespo, Ines Figueiredo, Ruth Riisnaes, Semini Sumanasuriya, Pasquale Rescigno, Zafeiris Zafeiriou, Adam Sharp, Nina Tunariu, Diletta Bianchini, Alexa Gillman, Christopher J Lord, Emma Hall, Arul M Chinnaiyan, Suzanne Carreira, Johann S de Bono
Biomarkers for a more precise patient care are needed in metastatic prostate cancer (mPC). We have reported a Phase II trial (TOPARP-A) of the poly(ADP)-ribose polymerase (PARP) inhibitor olaparib in mPC, demonstrating antitumor activity associating with homologous recombination DNA repair defects. We now report targeted and whole exome sequencing of serial circulating-free DNA (cfDNA) samples collected during this trial. Decreases in cfDNA concentration independently associated with outcome in multivariable analyses (HR for overall survival at week 8: 0...
April 27, 2017: Cancer Discovery
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